OpenOnco · Treatment Plan

Treatment plan — Invasive breast cancer

PLAN-BMA-ATM_GERMLINE_BREAST-V1 · v1 · 2026-08-18

Patient

BMA-ATM_GERMLINE_BREAST · Algorithm: ALGO-BREAST-1L

DiagnosisInvasive breast cancer

MOH / ICD-10C50

ICD-O-38500/3; C50.9

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
ESCAT: clinical review pendingBIO-HRR-PANEL	ATM germline pathogenic	IIA	Molecular evidence option SRC-CIVIC: Level A (Supports, Poor Outcome) SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	ATM germline pathogenic confers ~2× lifetime breast-cancer risk; no PARPi indication (TBCRC-048 ATM cohort showed minimal activity). Standard breast- cancer therapy by ER/HER2 status. ESCAT IIA (predisposition) / OncoKB Level 3A. Avoid radiotherapy in homozygous/biallelic ATM (radiosensitivity).	standard breast therapy by HR/HER2 enhanced screening (annual MRI)	SRC-NCCN-BREAST-2025 SRC-ESMO-BREAST-METASTATIC-2024
ESCAT: clinical review pendingBIO-HRR-PANEL	BARD1 germline pathogenic	IIA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response)	BARD1 germline pathogenic confers moderate breast-cancer risk (~2-3×). BARD1 forms heterodimer with BRCA1 → biological HR deficiency. Limited clinical PARPi data; off-label consideration. ESCAT IIA / OncoKB Level 3A.	standard breast therapy olaparib off-label (HRR rationale)	SRC-NCCN-BREAST-2025 SRC-ESMO-BREAST-METASTATIC-2024
ESCAT: clinical review pendingBIO-HRR-PANEL	BRIP1 germline pathogenic	IIIA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response)	BRIP1 germline pathogenic and breast cancer: weak/uncertain risk association (NCCN does not currently recommend enhanced breast surveillance based on BRIP1 alone). No PARPi indication. ESCAT IIIA / OncoKB Level 3B.	standard breast therapy by subtype	SRC-NCCN-BREAST-2025
ESCAT: clinical review pendingBIO-HRR-PANEL	CHEK2 germline pathogenic	IIA	SRC-NCCN-BREAST-2025 SRC-ESMO-BREAST-METASTATIC-2024 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	CHEK2 germline pathogenic (e.g. 1100delC) confers ~2× breast-cancer risk; no PARPi activity demonstrated (TBCRC-048 CHEK2 cohort minimal response). Standard HR/HER2-directed therapy. ESCAT IIA (predisposition) / OncoKB Level 3A.	standard breast therapy by subtype enhanced screening (annual MRI from age 40)	SRC-NCCN-BREAST-2025 SRC-ESMO-BREAST-METASTATIC-2024
ESCAT: clinical review pendingBIO-HRR-PANEL	PALB2 germline pathogenic	IIA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response)	PALB2 germline pathogenic confers BRCA-like breast risk (~50% lifetime). Olaparib activity reported in PALB2-mutated breast (Tung TBCRC-048: ORR ~82% in HER2-negative metastatic, n=11) but PARPi labels in breast remain BRCA- only. NCCN lists PALB2 as a PARPi-eligible mutation off-label. ESCAT IIA / OncoKB Level 3A.	olaparib (off-label per NCCN, TBCRC-048 evidence) talazoparib (off-label) platinum-based chemo (TNBC)	SRC-NCCN-BREAST-2025 SRC-ESMO-BREAST-METASTATIC-2024
ESCAT: clinical review pendingBIO-HRR-PANEL	RAD51B germline pathogenic	IIIA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response)	RAD51B germline pathogenic in breast: moderate-risk allele (~RR 2-4 for RAD51C/D, less established for RAD51B). No PARPi label; off-label consideration in HRD context. ESCAT IIB-IIIA / OncoKB Level 3B.	standard breast therapy PARPi off-label (HRD-positive context)	SRC-NCCN-BREAST-2025
ESCAT: clinical review pendingBIO-HRR-PANEL	RAD51C germline pathogenic	IIB	SRC-NCCN-BREAST-2025 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	RAD51C germline pathogenic in breast: moderate-risk allele (~RR 2-4 for RAD51C/D, less established for RAD51B). No PARPi label; off-label consideration in HRD context. ESCAT IIB-IIIA / OncoKB Level 3B.	standard breast therapy PARPi off-label (HRD-positive context)	SRC-NCCN-BREAST-2025
ESCAT: clinical review pendingBIO-HRR-PANEL	RAD51D germline pathogenic	IIB	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response)	RAD51D germline pathogenic in breast: moderate-risk allele (~RR 2-4 for RAD51C/D, less established for RAD51B). No PARPi label; off-label consideration in HRD context. ESCAT IIB-IIIA / OncoKB Level 3B.	standard breast therapy PARPi off-label (HRD-positive context)	SRC-NCCN-BREAST-2025
ESCAT: clinical review pendingBIO-HRR-PANEL	RAD54L germline pathogenic	IIIA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response)	RAD54L germline variants: rare; HR-pathway gene with limited clinical evidence. Included in some HRR panels but no labeled indication. ESCAT IIIA / OncoKB Level 4.	standard therapy PARPi off-label (HRD context only)	SRC-NCCN-BREAST-2025 SRC-ESMO-BREAST-METASTATIC-2024

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-BREAST-HR-POS-MET-1L-CDKI

Regimen

AI + ribociclib (HR+/HER2- metastatic 1L; OS-validated)

Drugs + NSZU

Letrozole (DRUG-LETROZOLE) 2.5 mg PO daily · Continuous · PO ✓ NSZU covered
Ribociclib (DRUG-RIBOCICLIB) 600 mg PO daily, days 1-21 of 28-day cycle · 21 days on, 7 days off · PO ⚠ NSZU — not for this indication

Supportive care

SUP-BONE-HEALTH-PROSTATE

Reason

Primary current-line option selected by ALGO-BREAST-1L at step 5.

Other current-line alternatives (8 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Standard plan

Indication

IND-BREAST-HR-POS-EARLY-ADJ-CDK46I

Regimen

Abemaciclib adjuvant (HR+/HER2- early high-risk breast cancer)

Drugs + NSZU

Abemaciclib (DRUG-ABEMACICLIB) 150 mg PO BID · Continuous BID x 2 years (fixed duration) · PO ⚠ NSZU — not for this indication

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB

Regimen

Ribociclib adjuvant + AI (HR+/HER2- early breast cancer; NATALEE)

Drugs + NSZU

Ribociclib (DRUG-RIBOCICLIB) 400 mg PO QD · Days 1-21 of each 28-day cycle (3 weeks on, 1 week off) · PO ⚠ NSZU — not for this indication
Letrozole (DRUG-LETROZOLE) 2.5 mg PO QD · Continuous (or anastrozole 1 mg QD or exemestane 25 mg QD as alternatives) · PO ✓ NSZU covered

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-BREAST-HER2-POS-EARLY-NEOADJUVANT

Regimen

TCHP — docetaxel + carboplatin + trastuzumab + pertuzumab (HER2+ neoadjuvant)

Drugs + NSZU

Docetaxel (DRUG-DOCETAXEL) 75 mg/m² IV · Day 1 of 21-day cycle x 6 cycles · IV ✓ NSZU covered
Carboplatin (DRUG-CARBOPLATIN) AUC 6 IV · Day 1 of 21-day cycle x 6 cycles · IV ⚠ NSZU — not for this indication
Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg IV loading, 6 mg/kg IV maintenance · Day 1 of 21-day cycle · IV ✓ NSZU covered
Pertuzumab (DRUG-PERTUZUMAB) 840 mg IV loading, 420 mg IV maintenance · Day 1 of 21-day cycle · IV ✓ NSZU covered

Supportive care

SUP-BONE-HEALTH-PROSTATE, SUP-G-CSF-PRIMARY-PROPHYLAXIS-PROSTATE

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-BREAST-HER2-POS-MET-1L-THP

Regimen

THP — docetaxel + trastuzumab + pertuzumab (HER2+ metastatic 1L)

Drugs + NSZU

Docetaxel (DRUG-DOCETAXEL) 75-100 mg/m² IV · Day 1 of 21-day cycle x 6-8 cycles, then HP maintenance · IV ✓ NSZU covered
Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg loading, 6 mg/kg maintenance IV · Day 1 of 21-day cycle, continuous until progression · IV ✓ NSZU covered
Pertuzumab (DRUG-PERTUZUMAB) 840 mg loading, 420 mg maintenance IV · Day 1 of 21-day cycle, continuous until progression · IV ✓ NSZU covered

Supportive care

SUP-BONE-HEALTH-PROSTATE

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-BREAST-HER2-POS-MET-2L-TDXD

Regimen

T-DXd monotherapy (HER2+ metastatic 2L+, also HER2-low metastatic)

Drugs + NSZU

Trastuzumab deruxtecan (T-DXd) (DRUG-TRASTUZUMAB-DERUXTECAN) 5.4 mg/kg IV · Day 1 of 21-day cycle, continuous until progression · IV ✓ NSZU covered

Supportive care

SUP-BONE-HEALTH-PROSTATE

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-BREAST-TNBC-EARLY-NEOADJUVANT

Regimen

Pembrolizumab + chemo (TNBC neoadjuvant)

Drugs + NSZU

Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3 weeks · Days 1 of cycles 1-8 (4 cycles each phase) · IV ⚠ NSZU — not for this indication
Paclitaxel (DRUG-PACLITAXEL) 80 mg/m² IV weekly · Cycles 1-4 (12 weekly doses) · IV ✓ NSZU covered
Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Cycles 1-4 q3 weeks (or weekly AUC 1.5) · IV ⚠ NSZU — not for this indication
Doxorubicin (DRUG-DOXORUBICIN) 60 mg/m² IV · Cycles 5-8 q3 weeks · IV ✓ NSZU covered
Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 600 mg/m² IV · Cycles 5-8 q3 weeks · IV ✓ NSZU covered

Supportive care

SUP-G-CSF-PRIMARY-PROPHYLAXIS-PROSTATE, SUP-BONE-HEALTH-PROSTATE

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-BREAST-BRCA-POS-MET-PARPI

Regimen

Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early)

Drugs + NSZU

Olaparib (DRUG-OLAPARIB) 300 mg PO BID continuous · Until progression (metastatic) or 1 year (OlympiA adjuvant) · PO ⚠ NSZU — not for this indication

Supportive care

SUP-BONE-HEALTH-PROSTATE

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO

Regimen

Pembrolizumab + chemotherapy (TNBC, metastatic PD-L1+)

Drugs + NSZU

Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV over 30 min · Day 1 q21d (when combined with paclitaxel or gem-carbo); or Day 1 q28d (when combined with nab-paclitaxel) · IV ⚠ NSZU — not for this indication

Reason

Current-line alternative presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Where to order	Needed for
TEST-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CECT-CAP	CECT chest/abdomen/pelvis	Critical	imaging	—	standard
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-ER-PR-IHC	ER + PR immunohistochemistry on tumor	Critical	—	CSD Lab ✓ (code TBC)	standard
TEST-HER2-IHC-FISH	HER2 IHC + reflex FISH on tumor	Critical	—	CSD Lab ✓ (code TBC)	standard
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	all tracks
TEST-BONE-SCAN	Whole-body Tc-99m MDP bone scintigraphy	Standard	—	—	standard
TEST-CT-CAP	CT chest/abdomen/pelvis	Standard	imaging	—	standard
TEST-ECG	Electrocardiogram	Standard	clinical_assessment	—	aggressive
TEST-ECHO	Echocardiography	Standard	imaging	—	all tracks
TEST-GERMLINE-BRCA-PANEL	Germline BRCA1/2 + HRR panel sequencing	Standard	—	CSD Lab: M089	standard
TEST-PIK3CA-NGS	PIK3CA mutation testing (tumor or ctDNA)	Standard	—	CSD Lab: M065	desired (standard)
TEST-TSH	Thyroid-stimulating hormone	Standard	lab	—	standard

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

ESR1 ligand-binding-domain hotspot Y537S or D538G — the two dominant hotspots (~70% of all ESR1-LBD mutations) acquired in HR+/HER2- metastatic breast progressing on aromatase inhibitor. EMERALD (Bidard 2022) randomized post-AI ± CDK4/6i HR+ MBC to elacestrant vs endocrine standard-of-care; PFS benefit was concentrated in the ESR1-mutant subgroup (mPFS 3.8 vs 1.9 mo, HR 0.55). Y537S is associated with more aggressive biology than D538G in some series. Candidate RF refines RF-BREAST-ESR1-MUT-ACTIONABLE for the predominant hotspots specifically targeted by elacestrant data.
Hotspot-specific narrowing of RF-BREAST-ESR1-MUT-ACTIONABLE. Y537S + D538G together account for ~70% of LBD mutations and are the hotspots most consistently represented in EMERALD subgroup analyses. Test on ctDNA at progression on AI ±…
RF-BREAST-ESR1-Y537S-D538G-CANDIDATESRC-NCCN-BREAST-2025SRC-ESMO-BREAST-METASTATIC-2024SRC-EMERALD-BIDARD-2022
Age ≥75 + ECOG ≥2 + significant comorbidity — anthracycline + dose-dense regimens poorly tolerated; consider TC, weekly paclitaxel, single-agent endocrine, or trastuzumab + chemo of reduced intensity.
Geriatric assessment (G8 / CGA) recommended pre-treatment for ≥70. HR+ disease in frail elderly may be managed with endocrine therapy alone (favorable risk-benefit). HER2+: trastuzumab + paclitaxel weekly or T-DM1 monotherapy…
RF-BREAST-FRAILTY-AGESRC-NCCN-BREAST-2025SRC-ESMO-BREAST-EARLY-2024
HBV/HCV/HIV serology + dental evaluation pre-bisphosphonate/denosumab + DPYD genotyping for capecitabine-containing regimens (EU practice).
Cross-disease HBV reactivation handled by RF-UNIVERSAL-HBV-REACTIVATION- RISK. DPYD deficiency screening unique to fluoropyrimidine-containing regimens; severe / fatal toxicity in homozygous deficient patients — EU/EMA-recommended pre-test.
RF-BREAST-INFECTION-SCREENINGSRC-NCCN-BREAST-2025SRC-ESMO-BREAST-EARLY-2024
Cardiac dysfunction (LVEF <50%) — anthracycline + trastuzumab/pertuzumab + T-DM1/T-DXd all carry cardiotoxicity risk; baseline echo + serial monitoring required.
Anthracycline + trastuzumab cumulative cardiotoxicity well-established. Modern strategies: cardio-oncology consult; substitute non-anthracycline regimen (TC for HER2-) or modified HER2-backbone if anthracycline contraindicated. T-DXd…
RF-BREAST-ORGAN-DYSFUNCTIONSRC-NCCN-BREAST-2025SRC-ESMO-BREAST-EARLY-2024
Somatic (tumor-only) BRCA1 or BRCA2 pathogenic variant identified on tumor NGS — pan-tumor PARPi-candidate signal. Disease applicability varies: ovarian (PAOLA-1, SOLO-1 — somatic BRCA pooled with germline in HRD-positive maintenance indication), mCRPC (PROfound cohort-A — olaparib mPFS 7.4 vs 3.6 mo, HR 0.34, somatic + germline pooled), pancreatic PDAC (POLO label is germline-only — somatic BRCA falls to off-label / NCCN "consider" tier), breast (OlympiAD / EMBRACA / OlympiA labels are germline-only — somatic BRCA breast remains investigational). Confirm somatic vs germline status via paired germline NGS before cascade-testing decisions (~40% of tumor-only "BRCA" calls are in fact germline per ASCO/CAP guidance).
Distinct trigger keys from RF-OVARIAN-BRCA-MUT-ACTIONABLE and RF-PROSTATE-HIGH-RISK-BIOLOGY to avoid double-firing on germline cases — this RF keys specifically on "*_somatic" / "tumor_*" findings. Breast included as informational (no…
RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATESRC-PROFOUND-DEBONO-2020SRC-NCCN-OVARIAN-2025SRC-NCCN-PROSTATE-2025

CONTRA-AGGRESSIVE

Hard contraindications to escalation

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Standard plan (IND-BREAST-HR-POS-EARLY-ADJ-CDK46I)

Do NOT use in pregnancy — CDK4/6i are teratogenic.
Do NOT start until full surgical wound healing.
Do NOT combine with strong CYP3A4 inhibitors — significant abemaciclib concentration increase.
Do NOT skip CBC monitoring q2w first 2 months — severe neutropenia risk.

Aggressive plan (IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB)

Do NOT use in pregnancy — CDK4/6i are teratogenic.
Do NOT start if baseline QTcF >450 ms — ribociclib prolongs QT interval (boxed warning; fatal arrhythmia risk).
Do NOT combine with strong CYP3A4 inhibitors (azole antifungals, clarithromycin, etc.) — significant ribociclib exposure increase.
Do NOT skip ECG/QTc monitoring (baseline, Day 14 Cycle 1, periodic thereafter) — fatal arrhythmia risk.
Do NOT use 600 mg dose adjuvantly — NATALEE protocol uses 400 mg; 600 mg is metastatic dosing only.

Standard plan (IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO)

НІКОЛИ не призначати пембролізумаб при CPS <10 — відсутня OS перевага; тільки токсичnoсть
Не призначати без тестування BRCA1/2 — BRCA-мутоваno пацієнти мають кращу відповідь на PARPi
Не використовувати атезолізумаб при TNBC — FDA відкликала реєстрацію у серпno 2021
Не застосовувати схему при стадії I-III (неоад'ювантnoй) — використовувати KEYNOTE-522 протокол

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · AI + ribociclib (HR+/HER2- metastatic 1L; OS-validated)

28-day cycles × Continuous until progression

Standard plan

Induction · Abemaciclib adjuvant (HR+/HER2- early high-risk breast cancer)

28-day cycles × 26 cycles (2 years fixed duration)

Aggressive plan

Induction · Ribociclib adjuvant + AI (HR+/HER2- early breast cancer; NATALEE)

28-day cycles × 36 cycles (3 years) for ribociclib; AI continues to 5 years

Standard plan

Induction · TCHP — docetaxel + carboplatin + trastuzumab + pertuzumab (HER2+ neoadjuvant)

21-day cycles × 6 (then surgery → adjuvant trastuzumab + pertuzumab to complete 1 year HER2-targeted therapy; T-DM1 if residual disease)

Standard plan

Induction · THP — docetaxel + trastuzumab + pertuzumab (HER2+ metastatic 1L)

21-day cycles × Docetaxel × 6-8; HP continues until progression

Standard plan

Induction · T-DXd monotherapy (HER2+ metastatic 2L+, also HER2-low metastatic)

21-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Pembrolizumab + chemo (TNBC neoadjuvant)

21-day cycles × 8 (paclitaxel/carbo+pembro phase 1-4, then AC+pembro phase 5-8)

Standard plan

Induction · Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early)

28-day cycles × Adjuvant: 12; Metastatic: continuous until progression

Standard plan

Induction · Pembrolizumab + chemotherapy (TNBC, metastatic PD-L1+)

28-day cycles × Pembrolizumab: up to 35 cycles (2 years) total or until progression/toxicity; chemo: typically 6-8 cycles then pembrolizumab maintenance

MDT brief

Discussion questions (6, 2 blocking)

OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist
BLOCKING OQ-BIOMARKER-ESTROGEN-RECEPTOR
What is the status of Estrogen receptor (ER) (BIO-ESTROGEN-RECEPTOR)? It is required by track(s): IND-BREAST-HR-POS-MET-1L-CDKI, IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB, IND-BREAST-TNBC-EARLY-NEOADJUVANT. Expected value: positive.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist
BLOCKING OQ-BIOMARKER-PROGESTERONE-RECEPTOR
What is the status of Progesterone receptor (PR) (BIO-PROGESTERONE-RECEPTOR)? It is required by track(s): IND-BREAST-HR-POS-MET-1L-CDKI. Expected value: positive.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist
OQ-BIOMARKER-BRCA-GERMLINE
What is the status of Germline BRCA1/2 mutation status (BIO-BRCA-GERMLINE)? It is required by track(s): IND-BREAST-BRCA-POS-MET-PARPI. Expected value: positive.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
OQ-BIOMARKER-HER2-SOLID
What is the status of HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB, IND-BREAST-HER2-POS-EARLY-NEOADJUVANT, IND-BREAST-HER2-POS-MET-1L-THP, IND-BREAST-HER2-POS-MET-2L-TDXD, IND-BREAST-TNBC-EARLY-NEOADJUVANT. Expected value: HER2 negative (IHC 0-1+ OR IHC 2+ FISH-negative).
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist
OQ-BIOMARKER-PDL1-CPS
What is the status of PD-L1 Combined Positive Score (CPS) (BIO-PDL1-CPS)? It is required by track(s): IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO. Expected value: CPS ≥10 by 22C3 pharmDx — required for OS benefit per KEYNOTE-355.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist

MDT talk tree (7 steps)

#	Owner	Topic	Action
1	pathologist	Biomarker status BLOCKING	What is the status of Estrogen receptor (ER) (BIO-ESTROGEN-RECEPTOR)? It is required by track(s): IND-BREAST-HR-POS-MET-1L-CDKI, IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB, IND-BREAST-TNBC-EARLY-NEOADJUVANT. Expected value: positive.
2	pathologist	Biomarker status BLOCKING	What is the status of Progesterone receptor (PR) (BIO-PROGESTERONE-RECEPTOR)? It is required by track(s): IND-BREAST-HR-POS-MET-1L-CDKI. Expected value: positive.
3	hematologist	Staging / disease burden	What is the current LDH? Marker of tumor burden and transformation.
4	molecular_geneticist	Biomarker status	What is the status of Germline BRCA1/2 mutation status (BIO-BRCA-GERMLINE)? It is required by track(s): IND-BREAST-BRCA-POS-MET-PARPI. Expected value: positive.
5	pathologist	Biomarker status	What is the status of HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB, IND-BREAST-HER2-POS-EARLY-NEOADJUVANT, IND-BREAST-HER2-POS-MET-1L-THP, IND-BREAST-HER2-POS-MET-2L-TDXD, IND-BREAST-TNBC-EARLY-NEOADJUVANT. Expected value: HER2 negative (IHC 0-1+ OR IHC 2+ FISH-negative).
6	pathologist	Biomarker status	What is the status of PD-L1 Combined Positive Score (CPS) (BIO-PDL1-CPS)? It is required by track(s): IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO. Expected value: CPS ≥10 by 22C3 pharmDx — required for OS benefit per KEYNOTE-355.
7	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (recommended) — for consideration (2)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-BRCA-GERMLINE

Data quality

Incomplete for default-track review. Default-track review is incomplete until required biomarker gaps are resolved.

Biomarker coverage: 0/5 known (0%), 5 missing, 2 default-track gaps
Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-ATM-CONFIRMED-CARRIER, RF-ATM-FAMILY-HISTORY-SUSPICION, RF-BARD1-CONFIRMED-CARRIER, RF-BARD1-FAMILY-HISTORY-SUSPICION, RF-BLM-CONFIRMED-CARRIER, RF-BRCA-CONFIRMED-CARRIER, RF-BRCA-HBOC-FAMILY-HISTORY-SUSPICION, RF-BREAST-AKT1-E17K-ACTIONABLE, RF-BREAST-AKT1-E17K-CAPIVASERTIB-CANDIDATE, RF-BREAST-BRCA-GERMLINE-ACTIONABLE, RF-BREAST-CDH1-LOBULAR-CANDIDATE, RF-BREAST-EARLY-STAGE, RF-BREAST-ESR1-MUT-ACTIONABLE, RF-BREAST-ESR1-Y537S-D538G-CANDIDATE, RF-BREAST-FRAILTY-AGE, RF-BREAST-HER2-AMP-ACTIONABLE, RF-BREAST-HER2-LOW-ACTIONABLE, RF-BREAST-HER2-ULTRALOW-CANDIDATE, RF-BREAST-HIGH-RISK-BIOLOGY, RF-BREAST-INFECTION-SCREENING, RF-BREAST-ORGAN-DYSFUNCTION, RF-BREAST-OVARIAN-HRD-ASSAY-DISTINCTION, RF-BREAST-PIK3CA-COALT-INAVOLISIB-CANDIDATE, RF-BREAST-PIK3CA-MUT-ACTIONABLE, RF-BREAST-STAGE-IV-METASTATIC, RF-BREAST-TNBC, RF-BREAST-TRANSFORMATION-PROGRESSION, RF-CASCADE-BRCA-FDR-POSITIVE, RF-CASCADE-LFS-FDR-POSITIVE, RF-CHEK2-CONFIRMED-CARRIER, RF-CHEK2-FAMILY-HISTORY-SUSPICION, RF-CHRONIC-SEVERE-OBESITY-BMI40-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, RF-HDGC-CDH1-CONFIRMED-CARRIER, RF-IATROGENIC-COMBINED-HRT-PREVENTION, RF-IATROGENIC-IODINE131-SECONDARY-PREVENTION, RF-IATROGENIC-LONG-TERM-HRMNL-CONTRACEPTION-PREVENTION, RF-IATROGENIC-PRIOR-RADIATION-PREVENTION, RF-LI-FRAUMENI-CONFIRMED-CARRIER, RF-LI-FRAUMENI-FAMILY-HISTORY-SUSPICION, RF-LIFESTYLE-ALCOHOL-CANCER-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-SEDENTARY-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-NBN-CONFIRMED-CARRIER, RF-NF1-CONFIRMED-CARRIER, RF-NF1-FAMILY-HISTORY-SUSPICION, RF-OCC-IONIZING-RADIATION-PREVENTION, RF-OCC-SHIFTWORK-CIRCADIAN-PREVENTION, RF-PALB2-CONFIRMED-CARRIER, RF-PALB2-FAMILY-HISTORY-SUSPICION, RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE, RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE, RF-PAN-PALB2-PARPI-CANDIDATE, RF-PEUTZ-JEGHERS-CONFIRMED-CARRIER, RF-PEUTZ-JEGHERS-FAMILY-HISTORY-SUSPICION, RF-RAD51C-D-CONFIRMED-CARRIER, RF-RAD51C-D-FAMILY-HISTORY-SUSPICION, RF-REPRODUCTIVE-BREAST-ENDOMETRIAL-PREVENTION, RF-REPRODUCTIVE-DES-IN-UTERO-EXPOSURE-PREVENTION, RF-REPRODUCTIVE-LATE-FIRST-PREGNANCY-PREVENTION, RF-REPRODUCTIVE-OCP-LONG-TERM

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-ESTROGEN-RECEPTOR`	Estrogen receptor (ER)	pathologist	yes	IND-BREAST-HR-POS-MET-1L-CDKI, IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB, IND-BREAST-TNBC-EARLY-NEOADJUVANT	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive
`BIO-PROGESTERONE-RECEPTOR`	Progesterone receptor (PR)	pathologist	yes	IND-BREAST-HR-POS-MET-1L-CDKI	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive
`BIO-BRCA-GERMLINE`	Germline BRCA1/2 mutation status	molecular_geneticist	no	IND-BREAST-BRCA-POS-MET-PARPI	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive
`BIO-HER2-SOLID`	HER2 status (solid tumors — gastric/GEJ/CRC scoring)	pathologist	no	IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB, IND-BREAST-HER2-POS-EARLY-NEOADJUVANT, IND-BREAST-HER2-POS-MET-1L-THP, IND-BREAST-HER2-POS-MET-2L-TDXD, IND-BREAST-TNBC-EARLY-NEOADJUVANT	Verify result, method, specimen, and report date before sign-off. Expected/constraint: HER2 negative (IHC 0-1+ OR IHC 2+ FISH-negative)
`BIO-PDL1-CPS`	PD-L1 Combined Positive Score (CPS)	pathologist	no	IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO	Verify result, method, specimen, and report date before sign-off. Expected/constraint: CPS ≥10 by 22C3 pharmDx — required for OS benefit per KEYNOTE-355

Technical MDT skill metadata (2/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).

Specialist	skill_id	Version	Last reviewed	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-DESTINY-BREAST03-CORTES-2022: Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer (2022)
SRC-ESMO-BREAST-EARLY-2024: ESMO Clinical Practice Guideline on Early Breast Cancer (2024)
SRC-ESMO-BREAST-METASTATIC-2024: ESMO Clinical Practice Guideline on Metastatic Breast Cancer (2024)
SRC-HER2CLIMB-MURTHY-2019: Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer (2019)
SRC-KEYNOTE-355-CORTES-2020: Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355) (2020)
SRC-KEYNOTE-522-SCHMID-2022: Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer (2022)
SRC-MONALEESA-2-HORTOBAGYI-2016: Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer (2016)
SRC-MONALEESA-3-SLAMON-2018: Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer (MONALEESA-3) (2018)
SRC-MONALEESA-7-TRIPATHY-2018: Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7) (2018)
SRC-MONARCHE-JOHNSTON-2023: Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial (2023)
SRC-NATALEE-SLAMON-2024: Ribociclib plus Endocrine Therapy in Early Breast Cancer (2024)
SRC-NCCN-BREAST-2025: NCCN Clinical Practice Guidelines — Breast Cancer (2025.v4)

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-08-18.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT06790264	Exploring the Tumor Micro-Environment with 68Ga-FAPi-46 PET/CT in Breast Cancer	NA	RECRUITING	European Institute of Oncology	—	Single country
NCT06716073	Long-Term Outcomes of Endoscopic-assisted vs Conventional Breast-conserving Surgery in Breast Cancer Patients After Neoadjuvant Therapy: a Randomized, Multicenter, Open Label, Non-inferiority Trial	NA	RECRUITING	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	—	Surrogate endpoint only Single country
NCT05861271	Adjuvant Pyrotinib and Capecitabine For HER2 Positive Micro Invasive Breast Cancer	PHASE2	RECRUITING	Fudan University	—	Surrogate endpoint only Single country
NCT06807502	Evaluation of Circulating Tumor Cells (CTC) Relevance in Breast Cancer Follow-up Using the ScreenCell Device	NA	RECRUITING	ScreenCell	—	Single country
NCT04790305	Effect of Huaier Granule on Adjuvant Treatment for High-risk Early-stage Triple-negative Breast Cancer	PHASE4	RECRUITING	Fudan University	—	Surrogate endpoint only Single country
NCT07003009	Immun Checkpoint Washout in Patients With Invasive Ductal Breast Cancer	NA	RECRUITING	Istanbul Training and Research Hospital	—	Small N (<50) Single country
NCT06823414	Endoscopy/Robotic Assisted Nipple Skin Sparing Mastectomy	N/A	RECRUITING	Alejandra García-Novoa	—	Single country
NCT03201861	Addition of Cisplatin to Adjuvant Chemotherapy for Early Stage Breast Cancer in High-Risk Women	PHASE3	RECRUITING	RenJi Hospital	—	Surrogate endpoint only Single country
NCT07260188	Organoids From Breast Cancer Patients Treated With Neoadjuvant Therapy	N/A	RECRUITING	Istituti Clinici Scientifici Maugeri SpA	—	Single country
NCT02945579	Multicenter Trial for Eliminating Breast Cancer Surgery or Radiotherapy in Exceptional Responders to Neoadjuvant Systemic Therapy	NA	RECRUITING	M.D. Anderson Cancer Center	—	Single country

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).

Option	UA registration	NSZU	Cost orientation	Access pathway
Standard plan AI + ribociclib (HR+/HER2- metastatic 1L; OS-validated) (REG-AI-RIBOCICLIB)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Abemaciclib adjuvant (HR+/HER2- early high-risk breast cancer) (REG-ABEMACICLIB-ADJUVANT)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Ribociclib adjuvant + AI (HR+/HER2- early breast cancer; NATALEE) (REG-RIBOCICLIB-AI-ADJUVANT)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan TCHP — docetaxel + carboplatin + trastuzumab + pertuzumab (HER2+ neoadjuvant) (REG-TCHP-NEOADJUVANT)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan THP — docetaxel + trastuzumab + pertuzumab (HER2+ metastatic 1L) (REG-THP-METASTATIC)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan T-DXd monotherapy (HER2+ metastatic 2L+, also HER2-low metastatic) (REG-TDXD-METASTATIC)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Pembrolizumab + chemo (TNBC neoadjuvant) (REG-PEMBRO-CHEMO-TNBC-NEOADJUVANT)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early) (REG-OLAPARIB-BREAST)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Pembrolizumab + chemotherapy (TNBC, metastatic PD-L1+) (REG-PEMBRO-CHEMO-TNBC-MET)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT06790264 Exploring the Tumor Micro-Environment with 68Ga-FAPi-46 PET/CT in Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06716073 Long-Term Outcomes of Endoscopic-assisted vs Conventional Breast-conserving Surgery in Breast Cancer Patients After Neoadjuvant Therapy: a Randomized, Multicenter, Open Label, Non-inferiority Trial No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05861271 Adjuvant Pyrotinib and Capecitabine For HER2 Positive Micro Invasive Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06807502 Evaluation of Circulating Tumor Cells (CTC) Relevance in Breast Cancer Follow-up Using the ScreenCell Device No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04790305 Effect of Huaier Granule on Adjuvant Treatment for High-risk Early-stage Triple-negative Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07003009 Immun Checkpoint Washout in Patients With Invasive Ductal Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06823414 Endoscopy/Robotic Assisted Nipple Skin Sparing Mastectomy No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT03201861 Addition of Cisplatin to Adjuvant Chemotherapy for Early Stage Breast Cancer in High-Risk Women No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07260188 Organoids From Breast Cancer Patients Treated With Neoadjuvant Therapy No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT02945579 Multicenter Trial for Eliminating Breast Cancer Surgery or Radiotherapy in Exceptional Responders to Neoadjuvant Systemic Therapy No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-18.

plan_id: PLAN-BMA-ATM_GERMLINE_BREAST-V1 | version: 1 | generated: 2026-08-18T07:59:48.948328+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.